Poly(ethylene glycol) (PEG) has long stood as the prevailing standard in drug delivery, celebrated for its capacity to enhance solubility, extend circulation, and improve pharmacological performance. Nevertheless, the emergence of anti-PEG antibodies, accelerated clearance, and limited biodegradability increasingly undermine its role as a universal solution. In response, a new generation of polymers has been developed to address these shortcomings, offering the potential to sustain or surpass PEG’s benefits while mitigating immunogenicity, improving biocompatibility, and enabling finer control over therapeutic fate. This review examines current research to articulate a coherent perspective on the replacement of PEG, tracing how advances in polymer design are reshaping the foundations of targeted drug delivery. Taken together, these developments signal not only a corrective to the limitations of PEG but also a broader paradigm shift toward safer, more versatile, and clinically translatable systems that define the next frontier in precision therapeutics.

The development of non-toxic silver nanoparticles (AgNPs) for medical and other diverse applications is steadily increasing. However, this study specifically aims to determine the cytotoxic effects of AgNPs synthesized via a green chemistry approach using aqueous-ethanol and ethyl acetate extracts of Artemisia terrae-albae. The photophysical, morphological, and size distribution characteristics of the synthesized AgNPs are analyzed using UV-Vis spectroscopy and transmission electron microscopy (TEM). A modified Allium cepa assay is employed to evaluate biological responses, including root growth, root number, and mitotic index. In this assay, the cell cycles of onion bulbs are synchronized and pre-incubated at 4 °C for 72 h prior to treatment. This study reveals that the AgNPs synthesized from the ethanol extract exhibit notable stability and higher cytotoxicity activity, with a root length of 0.6 ± 0.13 cm, root number of 16 ± 6.88, and mitotic index of 25.0 ± 2.6. These values are significantly more cytogenotoxic than those observed for the ethyl-acetate-derived nanoparticles, which show a root length of 0.8 ± 0.17 cm, root number of 18 ± 6.27, and mitotic index of 36 ± 3.6. These findings highlight the potential of green-synthesized AgNPs as effective cytotoxic agents, especially those obtained from ethanol extract, possibly due to a greater influence of the quantity of diverse phenolic compounds present in the complex mixtures than in the ethyl acetate extract, which otherwise enhanced their morphology, shape, and size. These, overall, contributed to the biological activity.

Poly(ethylene glycol) (PEG) has long stood as the prevailing standard in drug delivery, celebrated for its capacity to enhance solubility, extend circulation, and improve pharmacological performance. Nevertheless, the emergence of anti-PEG antibodies, accelerated clearance, and limited biodegradability increasingly undermine its role as a universal solution. In response, a new generation of polymers has been developed to address these shortcomings, offering the potential to sustain or surpass PEG’s benefits while mitigating immunogenicity, improving biocompatibility, and enabling finer control over therapeutic fate. This review examines current research to articulate a coherent perspective on the replacement of PEG, tracing how advances in polymer design are reshaping the foundations of targeted drug delivery. Taken together, these developments signal not only a corrective to the limitations of PEG but also a broader paradigm shift toward safer, more versatile, and clinically translatable systems that define the next frontier in precision therapeutics.